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Assignment 3: Alcohol Dependence
Overview: Alcohol dependence--a disease characterized by physical and emotional reliance on and overconsumption of alcohol--has long been known to have both a genetic and environmental interplay. Certain polymorphisms in a person's genome cause that individual to be more susceptible to alcohol dependency. People with polymorphisms in genes that regulate impulse control, dopamine and the brain's reward centers not only have greater chances of becoming reliant on alcohol, but may also experience severe withdrawal symptoms and other physiological conditions that typically characterize drug dependency. However, because alcohol is not an essential part of the diet, and can be avoided in life altogether, the research conducted on this disease has been somewhat nebulous. While scientists studying alcohol dependency have often focused on environmental factors that influence a person's alcohol consumption--such as peer group interactions and occupation--more recent work has elucidated specific genetic criteria that puts an individual at increased risk for becoming alcohol dependent. In essence, alcohol dependency (and alcoholism, the diagnostic term for alcohol dependency) is a unique disease in that, unlike other life-threatening illnesses, it is often self-inflicted and cannot occur without the "free will" to drink; one cannot become addicted to something to which he is never exposed. However, by understanding and identifying genomes that put an individual at higher risk for dependency, this disease can be better classified, understood, treated and avoided. Association Between Specific Genes and Alcohol Consumption: While it has been difficult for scientists to pinpoint precise genes that exclusively predispose someone to alcohol dependency, current research has found that genes that regulate and influence impulse control, brain chemistry and the liver's ability to process alcohol do have an affect on alcohol dependence. Moreover, a genetic basis is known because: "(1) there is a fourfold enhanced alcohol-dependence risk in relatives of alcoholics; (2) identical twins of alcohol-dependent subjects carry a higher risk for this disorder than do fraternal twins or full siblings; (3) the adopted children of alcoholics have the same fourfold enhanced risk for this disorder as do offspring raised by their alcohol-dependent parent (Goodwin et al., 1974; Cotton, 1979; Prescott and Kendler, 1999). The family and twin studies support the conclusion that the proportion of risk for this disorder explained by genes (that is, heritability) is between 40 and 60% (Prescott and Kendler, 1999; Schuckit et al., 2001)." Specifically, several studies have identified a polymorphism of the GABA-A receptor alpha 2 gene on chromosome 4 as being linked to phenotypes of impulsivity and disinhibition, which, in turn, seem to play a roll in how one responds to alcohol and how much alcohol is consumed by a person when in the presence of the substance. The natural function of GABA-A receptors is to reduce activity in the neurons to which they bind. GABA receptors control fear and anxiety, and in people with polymorphism of the GABA-A receptor alpha 2 gene on chromosome 4, alcohol can actually have an excessive, almost euphoric and highly-addictive affect, causing the individual to experience a kind of calm and "fearlessness" that would be naturally unparalleled in the absence of alcohol. Such a feeling can become something that an individual may crave (especially if he/she suffers from anxiety and other mood disorders, which oftentimes alcoholics do), thus beginning an addictive cycle. Another group of polymorphism in the genome that has been identified as playing a roll in alcohol dependency is the alcohol dehydrogenase 4 gene on chromosome 4 and the dopamine receptor D4 gene on chromosome 11. The latter causes changes to the dopamine reward systems by making the "high" one gets from alcohol much more intense for those with the polymorphism verses those without, and this high can be something to which both the human psyche and body become addicted. As for alcohol dehydrogenase, this is an enzyme that is responsible for breaking down and "digesting" alcohol. Those with a polymorphism causing decreased or inadequate production of the enzyme will be less likely (physically unable due to flush and feelings of illness) to imbibe large quantities of alcohol, while those with polymorphisms causing an abundant production of alcohol dehydrogenase can more quickly process alcohol, and thus can drink copious amounts without feeling the full effects of the alcohol. For the latter, such individuals will need more alcohol to feel "the high," thus increasing their tolerance and making for a greater likelihood of becoming addicted. The aforementioned polymorphisms illuminate the relationship between genotype and phenotype. A person's genotype--the genetic "endowment" of an individual--can influence whether the phenotype--a product of genotype and environment--will develop alcohol dependency. Essentially, in the way of alcoholism, genes and environment truly play equal roles. If a person with a genetic predisposition to alcohol dependency never has the opportunity (environment) to imbibe, he will not become alcohol dependent. Conversely, if a person with plentiful opportunities to drink has a genotype that makes him indifferent to alcohol (or, as in the case of alcohol dehydrogenase deficiency, unable to drink), then this person will also lack the "means" to become alcohol- dependent. Implications For Being At Higher Risk for Alcohol Dependency: Based upon the 23AndMe data gathered for John Burke, alcohol dependency is a ailment by which he has an increased risk of developing, as evidenced in the Health Summary. According to the study conducted by the Journal of General Psychology, "researchers compared 1,460 men with clinically-diagnosed alcohol dependence to 2,332 men without alcohol dependence, all of European ancestry. They found that each copy of a G at rs7590720 was associated with about 1.35 times higher odds of alcohol dependence" (Trutlein J et al). Since John Burke is genotppe GG, he is at moderately higher (1.50-2.49 times greater than average) risk for developing alcohol dependency. Thus, it would be wise for such an individual to be aware of his alcohol intake and his body's response to alcohol while drinking, or, if worried, consider abstaining from alcohol altogether. References: Edenberg et al., 2004; Lappalainen et al., 2005; Dick et al., 2006 Mayfield, R.D.Br J Pharmacol. May 2008; 154(2): 275–287. Published online Mar 24, 2008. McGill.edu: The Brain from Top-to-Bottom (2009) http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2442454/Treutlein J et al. (2009) . “Genome-wide association study of alcohol dependence.” Arch Gen Psychiatry 66(7):773-84. Images courtesy of Portland Alcohol Research Center